Is LCA5 p.Pro307Ala (c.919C>G) pathogenic?

LCA5 p.Pro307Ala (c.919C>G) is classified Conflicting classifications of pathogenicity in LCA5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0796); Rare (popmax 0.3%, afr); Associated with Inborn genetic diseases.

What condition is associated with LCA5 p.Pro307Ala (c.919C>G)?

LCA5 p.Pro307Ala (c.919C>G) is associated with Inborn genetic diseases (ClinVar).

How common is LCA5 p.Pro307Ala (c.919C>G) in the general population?

LCA5 p.Pro307Ala (c.919C>G) is rare (popmax 0.3%, afr) (gnomAD).

What do computational predictors say about LCA5 p.Pro307Ala (c.919C>G)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

LCA5 p.Pro307Ala

c.919C>G · rs139892282 · VCV707459

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.3%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.33, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 32 kb · p 0.58 · regional, not allelic
Overall
CADD	18.15	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.3% African / African-American · 222/73,890 alleles

Filtering AF 0.268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.255%

Overall 0.0164% 258/1,569,644 alleles · rare exomes 118/1,417,868 · genomes 140/151,776 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.3%	333
Middle Eastern	0.0349%	2,862
Remaining individualsnot grpmax-eligible	0.0346%	2,891
Admixed American	0.017%	5,878
South Asian	0.00228%	43,809
European (non-Finnish)	8.73e-05%	1,145,764

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: LCA5
Protein: p.Pro307Ala
Coding: c.919C>G
MANE Select: NM_001122769
dbSNP: rs139892282
Type: single nucleotide variant
Location: chr6:79492587 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.05

Full LCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LCA5 p.Pro307Thr Uncertain significance ★★ ⚠ same residue
LCA5 p.Ala107Thr Uncertain significance ★★ ⚠ same condition
LCA5 p.Ala425Pro Uncertain significance ★★ ⚠ same condition
LCA5 p.Ala683Pro Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg163His Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg174His Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg183Gln Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg213Gly Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/lca5-p-pro307ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown